Evaluation of expression profiles of microRNAs and two target genes, FOXO3a and RUNX2, effectively supports diagnostics and therapy predictions in breast cancer

Abstract

Breast cancer (BC) including its progression into bone metastasis is a complex process involving changes in gene expression and function of both, microRNAs (miRNAs) and their target genes. Deregulation of miRNAs has been described as a crucial factor responsible for the initiation and progression of BC, and specific miRNA expression profiles have been found to be associated with particular disease states, histological tumor types, and BRCA1/2 or HER status. BRCA1 tumor suppressor is involved in DNA damage response and repair and epigenetically controls miR-155 expression and its pre-cancerous potential. MiR-155 targets 3´UTR region of multiple components of the pro-oncogenic signaling cascades, including FOXO3a tumor suppressor and RUNX2 transcription factor regulating metastatic potential in BC. We employed qRT-PCR to determine expression level and examine possible regulatory role of selected miRNAs (miR-17, miR-18a, miR-19a, miR-20a, miR-21, miR-27a and miR-155) and their impact on expression modulation of FOXO3a and RUNX2 in peripheral blood mononuclear cells (PBMCs) in healthy individuals, in women carrying BRCA1 mutations with no disease manifestation, in women carrying BRCA1 mutations after tumor resection and therapy and in women with BC of unknown BRCA1 status in acute stage before tumor resection. Our results showed significant increase of miR-17, miR-19a, miR-21, miR-27, miR-155 and RUNX2 expression in PBMCs in BRCA1 patients and patients in acute stage, while FOXO3a expression was significantly decreased in these patients. MiR-18a and miR-20a expression was not affected. We propose that expressional changes reported in this study could provide significant additive information for early BC diagnosis, disease development prediction and therapy outcome monitoring.